Targeted temperature management at 33°C or 36℃ induces equivalent myocardial protection by inhibiting HMGB1 release in myocardial ischemia/reperfusion injury

Jin Ho Beom, Ju Hee Kim, Jeho Seo, Jung Ho Lee, Yong Eun Chung, Hyun Soo Chung, Sung Phil Chung, Chul Hoon Kim and Je Sung You

PLOS ONE, 2021, vol. 16, issue 1, 1-19

Abstract: Acute myocardial infarction (AMI) is lethal and causes myocardial necrosis via time-dependent ischemia due to prolonged occlusion of the infarct-related artery. No effective therapy or potential therapeutic targets can prevent myocardial ischemia/reperfusion (I/R) injury. Targeted temperature management (TTM) may reduce peri-infarct regions by inhibiting the extracellular release of high mobility group box-1 (HMGB1) as a primary mediator of the innate immune response. We used a rat left anterior descending (LAD) coronary artery ligation model to determine if TTM at 33°C and 36°C had similar myocardial protective effects. Rats were divided into sham, LAD I/R+37°C normothermia, LAD I/R+33°C TTM, and LAD I/R+36°C TTM groups (n = 5 per group). To verify the cardioprotective effect of TTM by specifically inhibiting HMGB1, rats were assigned to sham, LAD I/R, and LAD I/R after pre-treatment with glycyrrhizin (known as a pharmacological inhibitor of HMGB1) groups (n = 5 per group). Different target temperatures of 33°C and 36°C caused equivalent reductions in infarct volume after myocardial I/R, inhibited the extracellular release of HMGB1 from infarct tissue, and suppressed the expression of inflammatory cytokines from peri-infarct regions. TTM at 33°C and 36°C significantly attenuated the elevation of cardiac troponin, a sensitive and specific marker of heart muscle damage, after injury. Similarly, glycyrrhizin alleviated myocardial damage by suppressing the extracellular release of HMGB1. TTM at 33°C and 36°C had equivalent myocardial protective effects by similar inhibiting HMGB1 release against myocardial I/R injury. This is the first study to suggest that a target core temperature of 36°C is applicable for cardioprotection.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0246066

DOI: 10.1371/journal.pone.0246066

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